Plasma and urine levels of methotrexate and 7-hydroxymethotrexate in children with all during maintenance therapy with weekly oral methotrexate
✍ Scribed by Skoglund, Kathleen A. ;Söderhäll, Stefan ;Beck, Olof ;Peterson, Curt ;Wennberg, Mona ;Hayder, Salah ;Björk, Olle
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 599 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0098-1532
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✦ Synopsis
Abstract
A new high‐performance liquid chromatographic assay was used to determine methotrexate (MTX) and its main metabolite, 7‐hydroxymethotrexate (7‐OH‐MTX), in the plasma (n ‐ 17) and urine (n = 14) of children (age 3‐12 years) on maintenance therapy for acute lymphocytic leukemia (n = 14) or non‐Hodgkin's lymphoma (n = 3). Each child received oral doses of weekly MTX (4.0‐29 mg/m^2^) and daily 6‐mer‐captopurine (40‐111 mg/m^2^). Plasma samples were collected daily from two children during the 1‐week dose interval. A limited sampling strategy was designed, whereby 2 days of blood sampling were used in the other 15 patients. Morning urine samples were collected daily for 1 week following MTX intake from 14 of the children. MTX was detectable in all plasma and urine samples for the entire dose interval. The main metabolite, 7‐OH‐MTX, could be detected in plasma and urine from all patients on the first day after dose intake but only in a few patients during the whole dose interval. Interpatient variability of MTX and 7‐OH‐MTX levels was high at all points during the week. Significant correlation were found between the urinary MTX levels on days 2 and 7 and plasma MTX levels on day 2 after intake. No significant correlation was found between drug levels in plasma or urine and liver function tests in the children showing signs of mild liver injury. This assay provides a tool for further studies on the role of pharmacokinetics for the clinical effects of weekly oral low‐dose MTX given alone or in combination with 6‐mercaptopurine. © 1994 Wiley‐Liss, Inc.